Born in New York, Neufeld spent most of his youth in California (San Diego and San Francisco), and then moved back to New York City during his teenage years. He graduated from the High School of Music & Art in 1985 and Oberlin College with a B.A. in Art History in 1989.[1] Shortly after graduating from college, he spent over a year backpacking with his then-girlfriend (now his wife) through Southeast Asia and Central Europe, and living for a period in the Czech Republic.[1]

In 2005, shortly after Hurricane Katrina struck the Gulf Coast, Neufeld spent three weeks as an American Red Cross volunteer in Biloxi, Mississippi. The blog he kept about that experience turned into a self-published book, Katrina Came Calling (2006).[1] Later, Neufeld was asked to write the introduction to a book called Signs of Life: Surviving Katrina, a collection of photos of the hand-made signs that appeared in New Orleans and along the Gulf Coast following Hurricane Katrina. Profits from sales of the book went two organizations still working in the area: Common Ground Relief and Hands On Network.

In 2007–2008, Neufeld wrote and drew A.D.: New Orleans After the Deluge, an online graphic novel serialized on SMITH Magazine. A.D. tells the real stories of seven New Orleans residents and their experiences during and after Hurricane Katrina. A.D. received extensive press coverage, including in such venues as the Los Angeles Times,[7] the New Orleans Times-Picayune,[8] the Atlanta Journal-Constitution,[9]Rolling Stone, Wired.com,[10]BoingBoing,[11] the Toronto Star,[12] and National Public Radio's "News & Notes".

In May 2008, it was announced that a four-color hardcover edition of A.D. would be published by Pantheon Graphic Novels.[13] The book included 25% more story and art, as well as extensive revisions to the material from the webcomic.[14] Debuting on August 18, 2009, shortly before Hurricane Katrina's fourth anniversary, A.D. went on to become a New York Times bestseller.[15]

Neufeld is one of the founding members of the online comics collective ACT-I-VATE. In 2014 he joined the comics collective Hang Dai Editions (of whose founding members was his long-time friend Dean Haspiel).[16]

Neufeld co-wrote the "motion comics" element of the ABC News documentary Earth 2100, which premiered on ABC on June 2, 2009. Neufeld worked on the sections of the documentary dealing with the fictional character "Lucy," who witnesses the apocalyptic effects of climate change and societal upheaval during the course of the 21st century.[17]

Neufeld's collaborations with writers from outside the traditional comics world tend to be formalist and experimental in spirit. He has adapted a number of poet Nick Flynn's pieces into comics, which have appeared in various literary journals and websites.[24][25][26] Neufeld is an Associate Artist with the New York-based theatre collective The Civilians,[27] and has adapted portions of a number of their plays into comic book form. He has also collaborated with writer Eileen Myles,[28] and Neufeld's mother, artist Martha Rosler.[29][30] A special issue (subtitled "Of Two Minds") of Neufeld's comics series The Vagabonds was dedicated to his many collaborations.[31]

Most recently, Neufeld collaborated with journalist Brooke Gladstone, co-host of WNYC radio's On the Media. Their book, published by W.W. Norton, is titled The Influencing Machine[32] and was released in May 2011. Gladstone describes the book as "a treatise on the relationship between us and the news media, . . . a manifesto on the role of the press in American history as told through a cartoon version of [me] that would preside over each page."[33]